Downregulation of a mitochondria associated protein SLP-2 inhibits tumor cell motility, proliferation and enhances cell sensitivity to chemotherapeutic reagents

Cancer Biol Ther. 2009 Sep;8(17):1651-8. doi: 10.4161/cbt.8.17.9283. Epub 2009 Sep 17.

Abstract

Results from tissue microarray in this study and our previous reports revealed that stomatin-like protein 2 (SLP-2) is notably associated with tumorigenesis and metastasis. Many members of stomatin family are involved in tumor as mitochondrial component, and recent study has revealed that SLP-2 may also function in mitochondria. To further investigate the function of SLP-2, we used siRNA target SLP-2. Data showed that knock-down of SLP-2 potently inhibited cell motility, proliferation and slightly altered cell cycle without any significant change of apoptosis. Moreover, by combined application with different chemotherapeutic reagents, we observed the enhancement of cell chemosensitivity by SLP-2 depletion. We also confirmed that, SLP-2 localizes in mitochondria, affects mitochondrial membrane potential (MMP) and ATP production. We conclude that, SLP-2 is a mitochondrial protein and therefore, functions in energy process by MMP maintenance, and subsequently affecting cell motility, proliferation and chemosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics
  • Blood Proteins / genetics
  • Blood Proteins / metabolism*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Disease Progression
  • Down-Regulation
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Flow Cytometry
  • HeLa Cells
  • Humans
  • Lymphatic Metastasis
  • Membrane Potential, Mitochondrial / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Fluorescence
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Neoplasm Staging
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Survival Rate
  • Transfection

Substances

  • Antineoplastic Agents
  • Blood Proteins
  • Membrane Proteins
  • RNA, Small Interfering
  • STOML2 protein, human